How to divorce engaged chromosomes?
How to divorce engaged chromosomes?
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如何使接合的染色体分离？
DOI：
10.1128/mcb.25.1.18-22.2005
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发表时间：
2005
影响因子：
5.3
通讯作者：
Jessberger,Rolf
中科院分区：
文献类型：
--
作者：
Jessberger,Rolf
FEAR网络是有丝分裂和减数分裂进程所必需的，它激活磷酸酶Cdc14，而Cdc14是有丝分裂退出所必需的。然而，如果姐妹染色单体没有正确排列，即姐妹染色单体内聚没有在适当的时间建立和解决，则有丝分裂退出受到损害。这些过程需要内聚蛋白复合物及其破坏——至少对大多数染色体区域是这样。最近的两项研究描述了特定染色体片段的不寻常行为，如rRNA基因簇，其分离也需要依赖cdc14，不依赖黏结蛋白的途径。因此，控制染色体分离的机制比通常认为的更为多样化。在细胞周期的S期，新合成的姐妹染色单体开始接合。也就是说，它们进入内聚，在有丝分裂之前，它们物理地结合在一起并保持对齐。长期以来，姐妹染色单体是如何结合在一起的一直是个谜，是通过拓扑纠缠，还是通过粘在姐妹体上的强蛋白胶，还是通过包裹它们的蛋白质环。目前的证据可能支持环假说，即环状内聚蛋白复合物可能主要通过其封闭的结构（即拓扑结构）而不是作为结合两个DNA双链的粘合剂来阻止染色体的分离和分离（14）。内聚蛋白是一种四亚基蛋白复合物，其中SMC蛋白的异源二聚体（在本例中为SMC1/SMC3）与另外两种蛋白Scc1/RAD21/Mcd1和Scc3蛋白结合（图1A）。在脊椎动物中，sc3有两种变体，分别称为SA1和SA2。同样令人感兴趣的是如何及时分离这两个姐妹染色单体的问题。虽然近年来已经描述了通过修饰和破坏黏结蛋白复合体的一个组成部分来控制姐妹染色单体分离的一般机制（参见文献36），但很明显，除了黏结蛋白去除之外，还需要额外的途径来分离基因组的特定区域。
The FEAR network, which is required for mitotic and meiotic progression, activates the phosphatase Cdc14, known to be required for mitotic exit. Mitotic exit is impaired, however, if sister chromatids were not properly aligned, ie, if sister chromatid cohesion has not been established and resolved at the appropriate time. These processes require the cohesin complex and its destruction—at least for most of the chromosomal regions. Two recent studies describe an unusual behavior of particular chromosome segments such as the rRNA gene cluster, whose segregation also requires a CDC14-dependent, cohesin-independent pathway. Thus, mechanisms that govern chromosome segregation are more diverse than commonly assumed.During S phase of the cell cycle, the newly synthesized sister chromatids become engaged. That is, they enter into cohesion, where they are physically held together and remain aligned with each other until mitosis. It has long been a puzzle how the sister chromatids are held together, whether by topological entanglements, by a strong protein glue that sticks to both sisters, or by a protein ring that embraces them. Current evidence may favor the ring hypothesis, whereby a ring-like cohesin protein complex may prevent divorce and thus segregation of chromosomes, primarily by its closed structure, ie, topologically, rather than by acting as a cement bounding the two DNA duplices (14). Cohesin is a four-subunit protein complex, in which a heterodimer of SMC proteins, in this case SMC1/SMC3, associates with two other proteins, the Scc1/RAD21/Mcd1 and Scc3 proteins (Fig. 1A). In vertebrates there are two variants of Scc3, called SA1 and SA2. Equally intriguing is the question of how the timely segregation of the two sister chromatids is achieved. Although a general mechanism that governs sister chromatid segregation through modification and destruction of one component of the cohesin complex has been described in recent years (reviewed in reference 36), it has become clear that, in addition to cohesin removal, additional pathways are required for segregation of specific regions of the genome.